Difference between revisions of "Atypical hemolytic uremic syndrome"

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Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
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!colspan="4" align="center" style="color:white; font-size:125%; background-color:#31a354"|'''Section editors'''
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|style="width:35%"|<big>[[User:Shrutichaturvedi|Shruti Chaturvedi, MBBS, MSCI]]<br>Baltimore, MD</big><br>[https://www.linkedin.com/in/shruti-chaturvedi-bb83b126/ LinkedIn]
 
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|style="background-color:#F0F0F0; width:15%"|[[File:Tillman_Benjamin-2.jpg|frameless|upright=0.3|center]]
 
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|style="width:35%"|<big>[[User:Benjamintillman|Benjamin Tillman, MD]]<br>Nashville, TN</big>
 
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=All lines of therapy=
 
=All lines of therapy=
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==Eculizumab monotherapy {{#subobject:24195b|Regimen=1}}==
 
==Eculizumab monotherapy {{#subobject:24195b|Regimen=1}}==
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===Regimen {{#subobject:8ceb84|Variant=1}}===
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|<small>'''FDA-recommended dose'''</small>
 
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{| class="wikitable" style="width: 40%; text-align:center;"  
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===Regimen {{#subobject:8ceb84|Variant=1}}===
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!style="width: 25%"|Study
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{| class="wikitable" style="width: 100%; text-align:center;"  
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 50%"|Study
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!style="width: 50%"|[[Levels_of_Evidence#Evidence|Evidence]]
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|[https://doi.org/10.1056/NEJMoa1208981 Legendre et al. 2013 (C08-002)]
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|style="background-color:#91cf61"|Phase 2 (RT)
 
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|[https://www.nejm.org/doi/full/10.1056/NEJMoa1208981 Legendre et al. 2013 (C08-002)]
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|[https://doi.org/10.1056/NEJMoa1208981 Legendre et al. 2013 (C08-003)]
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|style="background-color:#91cf61"|Phase II
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|style="background-color:#91cf61"|Phase 2 (RT)
 
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|[https://www.nejm.org/doi/full/10.1056/NEJMoa1208981 Legendre et al. 2013 (C08-003)]
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449039/ Cofiell et al. 2015 (C10-004)]
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|style="background-color:#91cf61"|Phase II
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|style="background-color:#91cf61"|Non-randomized (RT)
 
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449039/ Cofiell et al. 2015]
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|[https://doi.org/10.1016/j.kint.2015.11.026 Greenbaum et al. 2016 (C10-003)]
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|style="background-color:#91cf61"|Non-randomized
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|style="background-color:#91cf61"|Phase 2
 
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''Eligible patients enrolled in Cofiell et al. 2015 had platelet counts less than 150 × 10<sup>9</sup>/L, hemoglobin levels less than or equal to the lower limit of normal, LDH levels greater than or equal to 1.5x upper limit of normal, serum creatinine levels greater than or equal to the upper limit of normal, ADAMTS13 activity greater than or equal to 5%, and no positive Shiga toxin-producing ''Escherichia coli'' test.''
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''Note: Eligible patients enrolled in C10-004 had platelet counts less than 150 x 10<sup>9</sup>/L, hemoglobin levels less than or equal to the lower limit of normal, LDH levels greater than or equal to 1.5x upper limit of normal, serum creatinine levels greater than or equal to the upper limit of normal, ADAMTS13 activity greater than or equal to 5%, and no positive Shiga toxin-producing ''Escherichia coli'' test.''
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<div class="toccolours" style="background-color:#b3e2cd">
 
====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
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*[[Eculizumab (Soliris)]] 900 mg IV once per week for 4 weeks, then 1200 mg IV once on week 5, then 1200 mg IV every 2 weeks
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*[[Eculizumab (Soliris)]] as follows:
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**Cycles 1 to 4: 900 mg IV once on day 1
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====Supportive medications====
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**Cycle 5 onwards: 1200 mg IV once on day 1
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====Supportive therapy====
 
* Patients were vaccinated against ''Neisseria meningitidis'' or received "appropriate antibiotics" if vaccination occurred within 14 days of the first dose
 
* Patients were vaccinated against ''Neisseria meningitidis'' or received "appropriate antibiotics" if vaccination occurred within 14 days of the first dose
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'''7-day cycle for 4 cycles, then 14-day cycles'''
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</div></div>
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===References===
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# '''C08-002:''' Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81. [https://doi.org/10.1056/NEJMoa1208981 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23738544/ PubMed] [https://clinicaltrials.gov/study/NCT00844545 NCT00844545]; [https://clinicaltrials.gov/study/NCT00844844 NCT00844844]
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# '''C08-003:''' Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81. [https://doi.org/10.1056/NEJMoa1208981 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23738544/ PubMed] [https://clinicaltrials.gov/study/NCT00838513 NCT00838513]; [https://clinicaltrials.gov/study/NCT00844428 NCT00844428]
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# '''C10-004:''' Cofiell R, Kukreja A, Bedard K, Yan Y, Mickle AP, Ogawa M, Bedrosian CL, Faas SJ. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood. 2015 May 21;125(21):3253-62. Epub 2015 Apr 1. [http://www.bloodjournal.org/content/125/21/3253.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449039/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25833956/ PubMed] [https://clinicaltrials.gov/study/NCT01194973 NCT01194973]
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# '''C10-003:''' Greenbaum LA, Fila M, Ardissino G, Al-Akash SI, Evans J, Henning P, Lieberman KV, Maringhini S, Pape L, Rees L, van de Kar NC, Vande Walle J, Ogawa M, Bedrosian CL, Licht C. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int. 2016 Mar;89(3):701-11. Epub 2016 Jan 28. [https://doi.org/10.1016/j.kint.2015.11.026 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26880462/ PubMed] [https://clinicaltrials.gov/study/NCT01193348 NCT01193348]
  
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'''Indefinite course'''
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==Ravulizumab monotherapy {{#subobject:abd213 |Regimen=1}}==
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<div class="toccolours" style="background-color:#eeeeee">
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===Regimen {{#subobject:8cehr3|Variant=1}}===
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{| class="wikitable" style="width: 40%; text-align:center;"
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!style="width: 25%"|Study
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!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
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|-
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|[https://doi.org/10.1016/j.kint.2020.01.035 Rondeau et al. 2020 (ALXN1210-aHUS-311)]
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|style="background-color:#91cf61"|Nonrandomized Phase 3
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|-
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7910247/ Tanaka et al. 2020 (ALXN1210-aHUS-312)]
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|style="background-color:#91cf61"|Nonrandomized Phase 3
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<div class="toccolours" style="background-color:#b3e2cd">
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====Immunosuppressive therapy====
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*[[Ravulizumab (Ultomiris)]]
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</div></div>
 
===References===
 
===References===
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# '''C08-002/C08-003:''' Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81. [https://www.nejm.org/doi/full/10.1056/NEJMoa1208981 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23738544 PubMed]
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#'''ALXN1210-aHUS-311:''' Rondeau E, Scully M, Ariceta G, Barbour T, Cataland S, Heyne N, Miyakawa Y, Ortiz S, Swenson E, Vallee M, Yoon SS, Kavanagh D, Haller H; 311 Study Group. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. Kidney Int. 2020 Jun;97(6):1287-1296. Epub 2020 Mar 6. Erratum in: Kidney Int. 2020 Dec;98(6):1621. Erratum in: Kidney Int. 2021 May;99(5):1244. [https://doi.org/10.1016/j.kint.2020.01.035 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32299680/ PubMed] [https://clinicaltrials.gov/study/NCT02949128 NCT02949128]
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# Cofiell R, Kukreja A, Bedard K, Yan Y, Mickle AP, Ogawa M, Bedrosian CL, Faas SJ. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood. 2015 May 21;125(21):3253-62. Epub 2015 Apr 1. [http://www.bloodjournal.org/content/125/21/3253.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449039/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25833956 PubMed]
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#'''ALXN1210-aHUS-312:''' Tanaka K, Adams B, Aris AM, Fujita N, Ogawa M, Ortiz S, Vallee M, Greenbaum LA. The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab. Pediatr Nephrol. 2021 Apr;36(4):889-898. Epub 2020 Oct 13. Erratum in: Pediatr Nephrol. 2020 Dec 9. [https://doi.org/10.1007/s00467-020-04774-2 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7910247/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33048203/ PubMed] [https://clinicaltrials.gov/study/NCT03131219 NCT03131219]
  
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[[Category:Atypical hemolytic-uremic syndrome (aHUS) regimens]]
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[[Category:Atypical hemolytic uremic syndrome regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:Complementopathies]]
 
[[Category:Complementopathies]]
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[[Category:Hemolytic disorders]]
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[[Category:Hemolytic process]]

Revision as of 12:09, 23 June 2024

Back to Top

Section editor
Tillman Benjamin-2.jpg
 Benjamin Tillman, MD
Vanderbilt University
Nashville, TN, USA
LinkedIn
  • We have moved How I Treat articles to a dedicated page.
2 regimens on this page
2 variants on this page


All lines of therapy

Eculizumab monotherapy

Regimen

FDA-recommended dose
Study Evidence
Legendre et al. 2013 (C08-002) Phase 2 (RT)
Legendre et al. 2013 (C08-003) Phase 2 (RT)
Cofiell et al. 2015 (C10-004) Non-randomized (RT)
Greenbaum et al. 2016 (C10-003) Phase 2

Note: Eligible patients enrolled in C10-004 had platelet counts less than 150 x 109/L, hemoglobin levels less than or equal to the lower limit of normal, LDH levels greater than or equal to 1.5x upper limit of normal, serum creatinine levels greater than or equal to the upper limit of normal, ADAMTS13 activity greater than or equal to 5%, and no positive Shiga toxin-producing Escherichia coli test.

Immunosuppressive therapy

  • Eculizumab (Soliris) as follows:
    • Cycles 1 to 4: 900 mg IV once on day 1
    • Cycle 5 onwards: 1200 mg IV once on day 1

Supportive therapy

  • Patients were vaccinated against Neisseria meningitidis or received "appropriate antibiotics" if vaccination occurred within 14 days of the first dose

7-day cycle for 4 cycles, then 14-day cycles

References

  1. C08-002: Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81. link to original article PubMed NCT00844545; NCT00844844
  2. C08-003: Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, Bingham C, Cohen DJ, Delmas Y, Douglas K, Eitner F, Feldkamp T, Fouque D, Furman RR, Gaber O, Herthelius M, Hourmant M, Karpman D, Lebranchu Y, Mariat C, Menne J, Moulin B, Nürnberger J, Ogawa M, Remuzzi G, Richard T, Sberro-Soussan R, Severino B, Sheerin NS, Trivelli A, Zimmerhackl LB, Goodship T, Loirat C. Terminal complement inhibitor eculizumab in atypical hemolytic uremic syndrome. N Engl J Med. 2013 Jun 6;368(23):2169-81. link to original article PubMed NCT00838513; NCT00844428
  3. C10-004: Cofiell R, Kukreja A, Bedard K, Yan Y, Mickle AP, Ogawa M, Bedrosian CL, Faas SJ. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood. 2015 May 21;125(21):3253-62. Epub 2015 Apr 1. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01194973
  4. C10-003: Greenbaum LA, Fila M, Ardissino G, Al-Akash SI, Evans J, Henning P, Lieberman KV, Maringhini S, Pape L, Rees L, van de Kar NC, Vande Walle J, Ogawa M, Bedrosian CL, Licht C. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int. 2016 Mar;89(3):701-11. Epub 2016 Jan 28. link to original article PubMed NCT01193348

Ravulizumab monotherapy

Regimen

Study Evidence
Rondeau et al. 2020 (ALXN1210-aHUS-311) Nonrandomized Phase 3
Tanaka et al. 2020 (ALXN1210-aHUS-312) Nonrandomized Phase 3

Immunosuppressive therapy

References

  1. ALXN1210-aHUS-311: Rondeau E, Scully M, Ariceta G, Barbour T, Cataland S, Heyne N, Miyakawa Y, Ortiz S, Swenson E, Vallee M, Yoon SS, Kavanagh D, Haller H; 311 Study Group. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment. Kidney Int. 2020 Jun;97(6):1287-1296. Epub 2020 Mar 6. Erratum in: Kidney Int. 2020 Dec;98(6):1621. Erratum in: Kidney Int. 2021 May;99(5):1244. link to original article PubMed NCT02949128
  2. ALXN1210-aHUS-312: Tanaka K, Adams B, Aris AM, Fujita N, Ogawa M, Ortiz S, Vallee M, Greenbaum LA. The long-acting C5 inhibitor, ravulizumab, is efficacious and safe in pediatric patients with atypical hemolytic uremic syndrome previously treated with eculizumab. Pediatr Nephrol. 2021 Apr;36(4):889-898. Epub 2020 Oct 13. Erratum in: Pediatr Nephrol. 2020 Dec 9. link to original article link to PMC article PubMed NCT03131219
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